AIM: Female sudden cardiac death may be more predictable

Sudden cardiac death (SCD) comprised the majority of 254 cardiac deaths among postmenopausal women with coronary artery disease (CAD), and the independent predictors of SCD improved its prediction when they were considered in addition to left ventricular ejection fraction (LVEF), based on a study published July 25 in the Archives of Internal Medicine.

SCD accounts for 250,000 to 300,000 deaths in the U.S. annually. Studies have suggested that SCD appears to be less common among women, and that the women who experience SCD are less likely than men to have had a history of clinical cardiovascular disease, evidence of structural heart disease or left ventricular dysfunction. While several studies have identified risk factors for SCD that include measures associated with CAD, none have specifically targeted the population of women with CAD.

Rajat Deo, MD, of the division of cardiovascular medicine at the University of Pennsylvania in Philadelphia, and colleagues addressed this gap in their study. Based on data of 2,763 postmenopausal women with CAD enrolled in the Heart and Estrogen/Progestin Replacement Study (HERS), the researchers evaluated the incidence of SCD in this population as well as its risk factors and predictive accuracy.

“Our first goal was to quantify SCD risk in this population and to compare it with risks for mortality from other cardiac and noncardiac conditions,” the authors wrote. “The second goal was to identify the most relevant risk factors for SCD among a large number of candidate variables using both traditional longitudinal methods and competing risk models. Finally, we determined the extent to which the identified risk factors could predict SCD risk and compared their incremental predictive value with prediction based on LVEF alone.”

The study provides a starting point for looking at risk prediction in the broader and understudied population of women with CAD and relatively preserved ejection fractions, wrote Christine M. Albert, MD, MPH, of the division of preventive medicine and cardiovascular medicine in the Center for Arrhythmia Prevention at Brigham and Women’s Hospital in Boston, in an accompanying editorial.

The HERS participants were postmenopausal women younger than 80 years with no previous hysterectomy and a history of at least one of the following: MI, CABG, PCI or angiographic narrowing of a coronary artery of more than 50 percent. They evaluated a series of baseline characteristics as potential risk factors for SCD, non-SCD, death from other causes and survivors.

Deo and colleagues found SCD comprised the majority of cardiac deaths among postmenopausal women with CAD, with SCD accounting for 54 percent (136 events) of the cardiac-related deaths and 27 percent of all deaths; with an annual event rate of 0.79 percent per year.The researchers noted that in clinical practice the only established predictor of SCD is severely decreased left ventricular systolic function, but that studies have suggested LVEF alone is insufficient for effective SCD risk prediction. They found six other independent predictors of SCD: MI, heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m2, atrial fibrillation, physical inactivity and diabetes.

Their analyses also showed that 25 percent of the HERS cohort had none of the seven risk factors; 44 percent had one risk factor, 22 percent had two risk factors, and 9 percent had three or more risk factors at baseline. SCD risk increased almost 10-fold across the four groups. Participants with no risk factors had an annualized SCD risk of 0.34 percent compared with 2.9 percent for those with at least three risk factors.

“The risk factors served as better predictors of SCD than LVEF alone and enhanced risk discrimination when both were combined,” they wrote. “A simple risk stratification based on the number of risk factors predicted a 10-fold gradient in the incidence of SCD.”

In her editorial, Albert noted that if confirmed, the risk categories may prove clinically useful. She advocated identifying and adding novel risk markers that specifically predict SCD into risk prediction algorithms.

“Although these data in isolation have uncertain clinical implications, Deo and colleagues’ study is an important step toward future research aimed at deriving and testing SCD risk prediction scores in broader populations,” she wrote. “Once validated and compared with existing risk stratification approaches in independent populations, these prediction algorithms could then be tested in future randomized trials.”

The research was supported through grants from the National Institutes of Health and the University of Pennsylvania.